NEWSFOCUS

the 35 million base-pair changes, 5 million indels in each species, and 689 extra genes in humans may have no functional meaning. To sort out the differences that matter from the ones that dont is really difficult, says Genomewise, humans and chimpanzees are quite similar, but studies are showing that David Haussler, a biomolecular engineer at they are not as similar as many tend to believe UC Santa Cruz, who has identified novel elements in the human genome that appear In a groundbreaking 1975 paper published provided the best validation yet of the 1% fig- to regulate genes (Science, 29 September in Science , evolutionary biologist Allan ure and the most dramatic evidence of its 2006, p. 1908). Daniel Geschwind, a neuroscientist at UC Wilson of the University of California (UC), limitations. The consortium researchers Berkeley, and his erstwhile graduate student aligned 2.4 billion bases from each species Los Angeles (UCLA), has taken at stab at Mary-Claire King made a convincing argu- and came up with a 1.23% difference. How- figuring out what matters by applying sysment for a 1% genetic difference between ever, as the chimpanzee consortium noted, tems biology to quantifying and analyzing humans and chimpanzees. At the time, that the figure reflects only base substitutions, genetic differences between human and was heretical, says King, now a medical not the many stretches of DNA that have chimpanzee brains. Working with his gradugeneticist at the University of Washington, been inserted or deleted in the genomes. ate student Michael Oldham and UCLA bioSeattle. Subsequent studies bore their conclu- The chimp consortium calculated that these statistician Steve Horvath, Geschwind comsion out, and today we take as a given that the indels, which can disrupt genes and pared which of 4000 genes were turned on at two species are genetically 99% the same. cause serious diseases such as cystic fibro- the same time, or coexpressed, in specific But truth be told, Wilson and King also sis, alone accounted for about a 3% addi- regions of the dissected brains. With these data, they built gene networks noted that the 1% difference wasnt the tional difference ( Science , 2 September for each species. A genes position in whole story. They predicted that there must 2005, p. 1468). a network has huge implications, be profound differences outside genes Entire genes are also routinely and ranGeschwind says. Genes that are they focused on gene regulationto domly duplicated or lost, further distinguishcoexpressed most frequently with account for the anatomical and behavioral ing humans from chimps. A team led by other genes have the most funcdisparities between our knuckletional relevance, he argues. dragging cousins and us. Several Human PRIMATE +689/86 Geschwind and his colleagues recent studies have proven them +870/1032 clustered the networks into seven perspicacious again, raising the Chimpanzee modules that correspond question of whether the 1% tru+26/729 to various brain regions, ism should be retired. such as the cortex. ComFor many, many years, the Mouse RODENT parisons of the map of 1% difference served us well +1405/562 each clusters network in because it was underappreciated +1773/378 Rat each species plainly how similar we were, says Pascal +1355/1120 showed that certain connections Gagneux, a zoologist at UC San exist in humans but not chimps. In Diego. Now its totally clear that Dog the cortex, for example, 17.4% of its more a hindrance for under+607/2165 the connections were specific to standing than a help. 17 6 93 87 humans, Geschwind and co-workers Using novel yardsticks and Millions of years before present reported in the 21 November 2006 the flood of sequence data now available for several species, The 6.4% difference. Throughout evolution, the gain (+) in the number of Proceedings of the National researchers have uncovered a copies of some genes and the loss () of others have contributed to human- Academy of Sciences . Although the differences dont immediately wide range of genomic features chimp differences. reveal why, say, humans get that may help explain why we walk upright and have bigger brainsand Matthew Hahn, who does computational Alzheimers and chimps dont, the maps why chimps remain resistant to AIDS and genomics at Indiana University, Blooming- clearly organize and prioritize differences. rarely miscarry. Researchers are finding that ton, has assessed gene gain and loss in the It really brings the critical hypotheses into on top of the 1% distinction, chunks of miss- mouse, rat, dog, chimpanzee, and human strong relief, says Geschwind. Could researchers combine all of whats ing DNA, extra genes, altered connections genomes. In the December 2006 issue of in gene networks, and the very structure of PLoS ONE, Hahn and co-workers reported known and come up with a precise percentage chromosomes confound any quantification that human and chimpanzee gene copy num- difference between humans and chimof humanness versus chimpness. There bers differ by a whopping 6.4%, concluding panzees? I dont think theres any way to calisnt one single way to express the genetic that gene duplication and loss may have culate a number, says geneticist Svante distance between two complicated living played a greater role than nucleotide substitu- Pbo, a chimp consortium member based at organisms, Gagneux adds. tion in the evolution of uniquely human phe- the Max Planck Institute for Evolutionary When King and the rest of the researchers notypes and certainly a greater role than has Anthropology in Leipzig, Germany. In the end, its a political and social and cultural thing in the Chimpanzee Sequencing and Analysis been widely appreciated. Consortium first detailed the genome of our Yet it remains a daunting task to link about how we see our differences. JON COHEN closest relative in 2005, they simultaneously genotype to phenotype. Many, if not most, of
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Relative Differences: The Myth of 1%

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SOURCE: J. P. DEMUTH ET AL.

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Most recent common ancestor